PGAP3 regulates human bronchial epithelial cell mRNAs present in asthma and respiratory virus reference data sets.

PGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase gene localized within chromosome 17q12-21, a region highly linked to asthma. Although much is known about the function of other chromosome 17q12-21 genes expressed at increased levels in bronchial epithelium such as ORMDL3 and GSDMB, little is known about the function of increased PGAP3 expression in bronchial epithelium in the context of asthma. The aim of this study was therefore to determine whether increased PGAP3 expression in human bronchial epithelial cells regulated expression of mRNA pathways important to the pathogenesis of asthma by utilizing RNA-sequencing and bioinformatic analysis.

Lymphotoxin beta receptor signaling directly controls airway smooth muscle deregulation and asthmatic lung dysfunction.

Background: Dysregulation of airway smooth muscle cells (ASM) is central to the severity of asthma. Which molecules dominantly control ASM in asthma is unclear. High levels of the cytokine LIGHT (aka TNFSF14) have been linked to asthma severity and lower baseline predicted FEV percentage, implying that signals through its receptors might directly control ASM dysfunction.

Single-base editing of rs12603332 on chromosome 17q21 with a cytosine base editor regulates ORMDL3 and ATF6α expression.

Background: Genetic association studies have demonstrated that the SNP rs12603332 located on chromosome 17q21 is highly associated with the risk of the development of asthma.

Methods: To determine whether SNP rs1260332 is functional in regulating levels of ORMDL3 expression, we used a Cytosine Base Editor (CBE) plasmid DNA or a CBE mRNA to edit the rs12603332 C risk allele to the T non-risk allele in a human lymphocyte cell line (i.e.

Integration of Clinical and Molecular Features into Prediction Models for Outcomes in Endometrial Cancer.

Endometrial cancer recurrence carries a poor prognosis. The rising incidence of endometrial cancer calls for improvements in treatment of advanced and recurrent diseases. Efforts have been made to molecularly characterize endometrial cancer with the goal of improving therapies.

An integrated prediction model of recurrence in endometrial endometrioid cancers.

Endometrial cancer incidence and mortality are rising in the US. Disease recurrence has been shown to have a significant impact on mortality. However, to date, there are no accurate and validated prediction models that would discriminate which individual patients are likely to recur.

Platelets attach to lung type 2 innate lymphoid cells (ILC2s) expressing P-selectin glycoprotein ligand 1 and influence ILC2 function.

Electron microscopy demonstrates that mouse lung ILC2 expressing PSGL-1 have platelets attached to their surface and that platelet depletion reduces lung ILC2 proliferation and Th2 cytokines suggesting ILC2 function is influenced by attachment to platelets.

A Prediction Model for Preoperative Risk Assessment in Endometrial Cancer Utilizing Clinical and Molecular Variables.

The utility of comprehensive surgical staging in patients with low risk disease has been questioned. Thus, a reliable means of determining risk would be quite useful. The aim of our study was to create the best performing prediction model to classify endometrioid endometrial cancer (EEC) patients into low or high risk using a combination of molecular and clinical-pathological variables.

Population Substructure Has Implications in Validating Next-Generation Cancer Genomics Studies with TCGA.

In the era of large genetic and genomic datasets, it has become crucially important to validate results of individual studies using data from publicly available sources, such as The Cancer Genome Atlas (TCGA). However, how generalizable are results from either an independent or a large public dataset to the remainder of the population? The study presented here aims to answer that question. Utilizing next generation sequencing data from endometrial and ovarian cancer patients from both the University of Iowa and TCGA, genomic admixture of each population was analyzed using STRUCTURE and ADMIXTURE software.

The miR-503 cluster is coordinately under-expressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes and chemotherapy response genes.

Background: The miR-503 miRNA cluster, located at Xq23.1, is composed of six miRNAs; miR-424, miR-503, miR-542, miR-450a-1, miR-450a-2 and miR-450b. Numerous studies have focused on the relationship of one or two members of the cluster and various human cancers.

Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases.

Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis.

Placenta-Specific Protein 1 Expression in Human Papillomavirus 16/18-Positive Cervical Cancers Is Associated With Tumor Histology.

Objective: Expression of the trophoblast-specific gene placenta-specific protein 1 (PLAC1) has been detected in a wide variety of cancers. However, to date, PLAC1 expression has not been shown in cervical cancer. We have carried out a preliminary study that shows for the first time that PLAC1 is expressed in cervical cancers.

β integrins rather than β integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung.

Background: Group 2 innate lymphoid cells (ILC2s) expand in the lungs of mice during type 2 inflammation induced by the fungal allergen Alternaria alternata. The increase in ILC2 numbers in the lung has been largely attributed to local proliferation and whether ILC2s migrate from the circulation to the lung after Alternaria exposure is unknown.

Objective: We examined whether human (lung, lymph node, and blood) and mouse lung ILC2s express β and β integrin adhesion molecules and whether these integrins are required for trafficking of ILC2s into the lungs of mice.

Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate.

In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium () to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen-challenged mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in and wild-type mice.